We have recently shown that NFATc1 is a nerve activity sensor in adult skeletal muscle and is involved in the maintenance of the slow muscle fiber type phenotype (McCullagh et al, 2004; Tothova et al, 2006). Our ongoing studies, using both in vivo transfection approaches and analysis of single fibers isolated from adult skeletal muscle, aim to establish: i) the origin of the Ca2+ signal responsible for the activation of the calcineurin-NFAT pathway; ii) the role of different NFAT isoforms; and iii) circadian rhythms in NFAT signalling.